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Concept of Moyamoya Disease

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Moyamoya Disease Explored Through RNF213

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Abstract

Moyamoya disease is characterized by progressive stenosis or occlusion of the major cerebral arteries, which often results in cerebral strokes. The concept of moyamoya disease was first proposed in Japan during the late 1960s. Recently, global recognition of this disease has increased. From a global perspective, this disease entity may be more appropriately classified as a syndrome that includes a broad spectrum of diseases of differing etiology sharing similar morphologies of the involved cerebral arteries. Indeed, current diagnosis depends on the morphological features of these cerebral arteries. However, it is often difficult to predict prognosis based upon cerebral artery morphology alone, and biomarkers are required in order to discern the various clinical phenotypes. The susceptibility gene RNF213 has been identified to have strong association with moyamoya diagnosis in East Asian patients and has proven useful as a clinical biomarker. Nevertheless, the trigger of the disease has yet to be clarified, and susceptibility genes have not been detected in non-Asian patients. Multiple common genetic variants and some secondary factors, including epigenetic factors, contribute to the development of the diverse clinical phenotypes of the disease. Therefore, deep phenotyping by proper stratification of heterogeneous populations using clinical, radiological, and biomarker patterns is essential in order to analyze individual etiological factors.

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References

  1. Kossorotoff M. Cognitive decline in Moyamoya: influence of chronic cerebral hypoxia, history of stroke, or comorbid conditions? Dev Med Child Neurol. 2012;54(1):5–6. doi:10.1111/j.1469-8749.2011.04159.x.

    Article  PubMed  Google Scholar 

  2. Kazumata K, Tha KK, Narita H, Kusumi I, Shichinohe H, Ito M, Nakayama N, Houkin K. Chronic ischemia alters brain microstructural integrity and cognitive performance in adult Moyamoya disease. Stroke. 2015;46(2):354–60. doi:10.1161/STROKEAHA.114.007407.

    Article  CAS  PubMed  Google Scholar 

  3. Kuroda S, Houkin K. Moyamoya disease: current concepts and future perspectives. Lancet Neurol. 2008;7(11):1056–66. doi:10.1016/S1474-4422(08)70240-0.

    Article  PubMed  Google Scholar 

  4. Kuroda S, Hashimoto N, Yoshimoto T, Iwasaki Y, Research Committee on Moyamoya Disease in J. Radiological findings, clinical course, and outcome in asymptomatic Moyamoya disease: results of multicenter survey in Japan. Stroke. 2007;38(5):1430–5. doi:10.1161/STROKEAHA.106.478297.

    Article  PubMed  Google Scholar 

  5. Research Committee on the Pathology, Treatment of Spontaneous Occlusion of the Circle of Willis, Health Labour Sciences Research Grant for Research on Measures for Infractable Diseases. Guidelines for diagnosis and treatment of Moyamoya disease (spontaneous occlusion of the circle of Willis). Neurol Med Chir (Tokyo). 2012;52(5):245–66.

    Article  Google Scholar 

  6. Uchino H, Kim JH, Fujima N, Kazumata K, Ito M, Nakayama N, Kuroda S, Houkin K. Synergistic interactions between direct and indirect bypasses in combined procedures: the significance of indirect bypasses in Moyamoya disease. Neurosurgery. 2016; doi:10.1227/NEU.0000000000001201.

    PubMed  Google Scholar 

  7. Takeuchi KSK. Hypoplasia of the bilateral internal carotid arteries. Brain Nerve. 1957;9:37–43.

    Google Scholar 

  8. Suzuki J, Takaku A. Cerebrovascular “Moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969;20(3):288–99.

    Article  CAS  PubMed  Google Scholar 

  9. Miyawaki S, Imai H, Shimizu M, Yagi S, Ono H, Mukasa A, Nakatomi H, Shimizu T, Saito N. Genetic variant RNF213 c.14576G>A in various phenotypes of intracranial major artery stenosis/occlusion. Stroke. 2013;44(10):2894–7. doi:10.1161/STROKEAHA.113.002477.

    Article  CAS  PubMed  Google Scholar 

  10. Fujimura M, Tominaga T. Lessons learned from Moyamoya disease: outcome of direct/indirect revascularization surgery for 150 affected hemispheres. Neurol Med Chir (Tokyo). 2012;52(5):327–32.

    Article  Google Scholar 

  11. Czabanka M, Pena-Tapia P, Schubert GA, Heppner FL, Martus P, Horn P, Schmiedek P, Vajkoczy P. Proposal for a new grading of Moyamoya disease in adult patients. Cerebrovasc Dis. 2011;32(1):41–50. doi:10.1159/000326077.

    Article  CAS  PubMed  Google Scholar 

  12. Houkin K, Ito M, Sugiyama T, Shichinohe H, Nakayama N, Kazumata K, Kuroda S. Review of past research and current concepts on the etiology of Moyamoya disease. Neurol Med Chir (Tokyo). 2012;52(5):267–77.

    Article  Google Scholar 

  13. Phi JH, Wang KC, Lee JY, Kim SK. Moyamoya syndrome: A window of Moyamoya disease. J Korean Neurosurg Soc. 2015;57(6):408–14. doi:10.3340/jkns.2015.57.6.408.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Guey S, Tournier-Lasserve E, Herve D, Kossorotoff M. Moyamoya disease and syndromes: from genetics to clinical management. Appl Clin Genet. 2015;8:49–68. doi:10.2147/TACG.S42772.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Komiyama M, Nishikawa M, Yasui T, Otsuka M, Haze K. Moyamoya disease and coronary artery disease–case report. Neurol Med Chir (Tokyo). 2001;41(1):37–41.

    Article  CAS  Google Scholar 

  16. Goto Y, Yonekawa Y. Worldwide distribution of Moyamoya disease. Neurol Med Chir (Tokyo). 1992;32(12):883–6.

    Article  CAS  Google Scholar 

  17. Uchino K, Johnston SC, Becker KJ, Tirschwell DL. Moyamoya disease in Washington state and California. Neurology. 2005;65(6):956–8. doi:10.1212/01.wnl.0000176066.33797.82.

    Article  PubMed  Google Scholar 

  18. Yonekawa Y, Ogata N, Kaku Y, Taub E, Imhof HG. Moyamoya disease in Europe, past and present status. Clin Neurol Neurosurg. 1997;99(Suppl 2):S58–60.

    Article  PubMed  Google Scholar 

  19. Kainth D, Chaudhry SA, Kainth H, Suri FK, Qureshi AI. Epidemiological and clinical features of Moyamoya disease in the USA. Neuroepidemiology. 2013;40(4):282–7. doi:10.1159/000345957.

    Article  PubMed  Google Scholar 

  20. Kraemer M, Heienbrok W, Berlit P. Moyamoya disease in Europeans. Stroke. 2008;39(12):3193–200. doi:10.1161/STROKEAHA.107.513408.

    Article  PubMed  Google Scholar 

  21. Acker G, Goerdes S, Schneider UC, Schmiedek P, Czabanka M, Vajkoczy P. Distinct clinical and radiographic characteristics of Moyamoya disease amongst European Caucasians. Eur J Neurol. 2015;22(6):1012–7. doi:10.1111/ene.12702.

    Article  CAS  PubMed  Google Scholar 

  22. Fukui M, Kono S, Sueishi K, Ikezaki K. Moyamoya disease. Neuropathology. 2000;20(Suppl):S61–4.

    Article  PubMed  Google Scholar 

  23. Takekawa Y, Umezawa T, Ueno Y, Sawada T, Kobayashi M. Pathological and immunohistochemical findings of an autopsy case of adult Moyamoya disease. Neuropathology. 2004;24(3):236–42.

    Article  PubMed  Google Scholar 

  24. Masuda J, Ogata J, Yutani C. Smooth muscle cell proliferation and localization of macrophages and T cells in the occlusive intracranial major arteries in Moyamoya disease. Stroke. 1993;24(12):1960–7.

    Article  CAS  PubMed  Google Scholar 

  25. Kaku Y, Morioka M, Ohmori Y, Kawano T, Kai Y, Fukuoka H, Hirai T, Yamashita Y, Kuratsu J. Outer-diameter narrowing of the internal carotid and middle cerebral arteries in Moyamoya disease detected on 3D constructive interference in steady-state MR image: is arterial constrictive remodeling a major pathogenesis? Acta Neurochir. 2012;154(12):2151–7. doi:10.1007/s00701-012-1472-4.

    Article  PubMed  Google Scholar 

  26. Hosoda Y, Ikeda E, Hirose S. Histopathological studies on spontaneous occlusion of the circle of Willis (cerebrovascular Moyamoya disease). Clin Neurol Neurosurg. 1997;99(Suppl 2):S203–8.

    Article  PubMed  Google Scholar 

  27. Blecharz KG, Frey D, Schenkel T, Prinz V, Bedini G, Krug SM, Czabanka M, Wagner J, Fromm M, Bersano A, Vajkoczy P. Autocrine release of angiopoietin-2 mediates cerebrovascular disintegration in Moyamoya disease. J Cereb Blood Flow Metab. 2016; doi:10.1177/0271678X16658301.

    PubMed  Google Scholar 

  28. Hitomi T, Habu T, Kobayashi H, Okuda H, Harada KH, Osafune K, Taura D, Sone M, Asaka I, Ameku T, Watanabe A, Kasahara T, Sudo T, Shiota F, Hashikata H, Takagi Y, Morito D, Miyamoto S, Nakao K, Koizumi A. Downregulation of Securin by the variant RNF213 R4810K (rs112735431, G>A) reduces angiogenic activity of induced pluripotent stem cell-derived vascular endothelial cells from Moyamoya patients. Biochem Biophys Res Commun. 2013;438(1):13–9. doi:10.1016/j.bbrc.2013.07.004.

    Article  CAS  PubMed  Google Scholar 

  29. Koizumi A, Kobayashi H, Hitomi T, Harada KH, Habu T, Youssefian S. A new horizon of Moyamoya disease and associated health risks explored through RNF213. Environ Health Prev Med. 2016;21(2):55–70. doi:10.1007/s12199-015-0498-7.

    Article  CAS  PubMed  Google Scholar 

  30. Kobayashi H, Matsuda Y, Hitomi T, Okuda H, Shioi H, Matsuda T, Imai H, Sone M, Taura D, Harada KH, Habu T, Takagi Y, Miyamoto S, Koizumi A. Biochemical and functional characterization of RNF213 (Mysterin) R4810K, a susceptibility mutation of Moyamoya disease, in angiogenesis in vitro and in vivo. J Am Heart Assoc. 2015;4(7) doi:10.1161/JAHA.115.002146.

  31. Achrol AS, Guzman R, Lee M, Steinberg GK. Pathophysiology and genetic factors in Moyamoya disease. Neurosurg Focus. 2009;26(4):E4. doi:10.3171/2009.1.FOCUS08302.

    Article  PubMed  Google Scholar 

  32. Psaltis PJ, Simari RD. Vascular wall progenitor cells in health and disease. Circ Res. 2015;116(8):1392–412. doi:10.1161/CIRCRESAHA.116.305368.

    Article  CAS  PubMed  Google Scholar 

  33. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7.

    Article  CAS  PubMed  Google Scholar 

  34. Kang HS, Moon YJ, Kim YY, Park WY, Park AK, Wang KC, Kim JE, Phi JH, Lee JY, Kim SK. Smooth-muscle progenitor cells isolated from patients with Moyamoya disease: novel experimental cell model. J Neurosurg. 2014;120(2):415–25. doi:10.3171/2013.9.JNS131000.

    Article  CAS  PubMed  Google Scholar 

  35. Sugiyama T, Kuroda S, Nakayama N, Tanaka S, Houkin K. Bone marrow-derived endothelial progenitor cells participate in the initiation of Moyamoya disease. Neurol Med Chir (Tokyo). 2011;51(11):767–73.

    Article  Google Scholar 

  36. Hojo M, Hoshimaru M, Miyamoto S, Taki W, Nagata I, Asahi M, Matsuura N, Ishizaki R, Kikuchi H, Hashimoto N. Role of transforming growth factor-beta1 in the pathogenesis of Moyamoya disease. J Neurosurg. 1998;89(4):623–9. doi:10.3171/jns.1998.89.4.0623.

    Article  CAS  PubMed  Google Scholar 

  37. Houkin K, Yoshimoto T, Abe H, Nagashima K, Nagashima M, Takeda M, Isu T. Role of basic fibroblast growth factor in the pathogenesis of Moyamoya disease. Neurosurg Focus. 1998;5(5):e2.

    Article  CAS  PubMed  Google Scholar 

  38. Nanba R, Kuroda S, Ishikawa T, Houkin K, Iwasaki Y. Increased expression of hepatocyte growth factor in cerebrospinal fluid and intracranial artery in Moyamoya disease. Stroke. 2004;35(12):2837–42. doi:10.1161/01.STR.0000148237.13659.e6.

    Article  CAS  PubMed  Google Scholar 

  39. Fujimura M, Watanabe M, Narisawa A, Shimizu H, Tominaga T. Increased expression of serum Matrix Metalloproteinase-9 in patients with Moyamoya disease. Surg Neurol. 2009;72(5):476–80. discussion 480 doi:10.1016/j.surneu.2008.10.009.

    Article  PubMed  Google Scholar 

  40. Kang HS, Kim JH, Phi JH, Kim YY, Kim JE, Wang KC, Cho BK, Kim SK. Plasma matrix metalloproteinases, cytokines and angiogenic factors in Moyamoya disease. J Neurol Neurosurg Psychiatry. 2010;81(6):673–8. doi:10.1136/jnnp.2009.191817.

    Article  PubMed  Google Scholar 

  41. Bersano A, Guey S, Bedini G, Nava S, Herve D, Vajkoczy P, Tatlisumak T, Sareela M, van der Zwan A, Klijn CJ, Braun KP, Kronenburg A, Acerbi F, Brown MM, Calviere L, Cordonnier C, Henon H, Thines L, Khan N, Czabanka M, Kraemer M, Simister R, Prontera P, Tournier-Lasserve E, Parati E, European Moyamoya Disease I. Research progresses in understanding the pathophysiology of Moyamoya disease. Cerebrovasc Dis. 2016;41(3–4):105–18. doi:10.1159/000442298.

    Article  PubMed  Google Scholar 

  42. Kamada F, Aoki Y, Narisawa A, Abe Y, Komatsuzaki S, Kikuchi A, Kanno J, Niihori T, Ono M, Ishii N, Owada Y, Fujimura M, Mashimo Y, Suzuki Y, Hata A, Tsuchiya S, Tominaga T, Matsubara Y, Kure S. A genome-wide association study identifies RNF213 as the first Moyamoya disease gene. J Hum Genet. 2011;56(1):34–40. doi:10.1038/jhg.2010.132.

    Article  CAS  PubMed  Google Scholar 

  43. Liu W, Morito D, Takashima S, Mineharu Y, Kobayashi H, Hitomi T, Hashikata H, Matsuura N, Yamazaki S, Toyoda A, Kikuta K, Takagi Y, Harada KH, Fujiyama A, Herzig R, Krischek B, Zou L, Kim JE, Kitakaze M, Miyamoto S, Nagata K, Hashimoto N, Koizumi A. Identification of RNF213 as a susceptibility gene for Moyamoya disease and its possible role in vascular development. PLoS One. 2011;6(7):e22542. doi:10.1371/journal.pone.0022542.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Liu W, Senevirathna ST, Hitomi T, Kobayashi H, Roder C, Herzig R, Kraemer M, Voormolen MH, Cahova P, Krischek B, Koizumi A. Genomewide association study identifies no major founder variant in Caucasian Moyamoya disease. J Genet. 2013;92(3):605–9.

    Article  PubMed  Google Scholar 

  45. Ganesan V, Smith ER. Moyamoya: defining current knowledge gaps. Dev Med Child Neurol. 2015;57(9):786–7. doi:10.1111/dmcn.12708.

    Article  PubMed  Google Scholar 

  46. Bush AM, Borzage MT, Choi S, Vaclavu L, Tamrazi B, Nederveen AJ, Coates TD, Wood JC. Determinants of resting cerebral blood flow in sickle cell disease. Am J Hematol. 2016;91(9):912–7. doi:10.1002/ajh.24441.

    Article  CAS  PubMed  Google Scholar 

  47. Sensenbach W, Madison L, Eisenberg S, Ochs L. The cerebral circulation and metabolism in hyperthyroidism and myxedema. J Clin Invest. 1954;33(11):1434–40. doi:10.1172/JCI103021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Dai D, Lu Q, Huang Q, Yang P, Hong B, Xu Y, Zhao W, Liu J, Li Q. Serum miRNA signature in Moyamoya disease. PLoS One. 2014;9(8):e102382. doi:10.1371/journal.pone.0102382.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Zhao S, Gong Z, Zhang J, Xu X, Liu P, Guan W, Jing L, Peng T, Teng J, Jia Y. Elevated Serum MicroRNA Let-7c in Moyamoya disease. J Stroke Cerebrovasc Dis. 2015;24(8):1709–14. doi:10.1016/j.jstrokecerebrovasdis.2015.01.041.

    Article  PubMed  Google Scholar 

  50. Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell. 2007;128(4):635–8. doi:10.1016/j.cell.2007.02.006.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Kita 15 Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Haruto Uchino, Ken Kazumata & Kiyohiro Houkin

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  1. Haruto Uchino
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  2. Ken Kazumata
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  3. Kiyohiro Houkin
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Correspondence to Haruto Uchino .

Editor information

Editors and Affiliations

  1. Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Akio Koizumi

  2. Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan

    Kazuhiro Nagata

  3. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Kiyohiro Houkin

  4. Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan

    Teiji Tominaga

  5. Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Susumu Miyamoto

  6. Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan

    Shigeo Kure

  7. CHU Paris‐GH St‐Louis Lariboisière F‐Widal, Hôpital Lariboisière, Paris, France

    Elizabeth Tournier-Lasserve

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Uchino, H., Kazumata, K., Houkin, K. (2017). Concept of Moyamoya Disease. In: Koizumi, A., et al. Moyamoya Disease Explored Through RNF213. Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-10-2711-6_2

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  • DOI: https://doi.org/10.1007/978-981-10-2711-6_2

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